5-HT receptor

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT.^[1] 5-HT receptors are located on the cell membrane of nerve cells and other cell types including smooth muscle in animals, and mediate the effects of serotonin as the endogenous ligand and of a broad range of pharmaceutical and hallucinogenic drugs. 5-HT receptors affect the release and activity of other neurotransmitters such as glutamate, dopamine and GABA. 5-HT_2A receptors increase the activity of glutamate in many areas of the brain, while some other serotonin receptors have the effect of suppressing glutamate. Increased stimulation of 5-HT_2A receptors seem to oppose the therapeutic actions of increased stimulation of other serotonin receptors in anti-depressant and anxiolytic treatments.^[2]

Classification

With the exception of the 5-HT₃ receptor, a ligand gated ion channel, all other 5-HT receptors are G protein coupled seven transmembrane (or heptahelical) receptors that activate an intracellular second messenger cascade.

Families

Family	Type	Mechanism
5-HT₁	G_i/G_o coupled	decreasing cellular levels of cAMP
5-HT₂	G_q/G₁₁ coupled	increasing cellular levels of inositol trisphosphate (IP₃) and diacylglycerol (DAG)
5-HT₃	ligand-gated Na⁺ and K⁺ cation channel	depolarizing plasma membrane
5-HT₄	G_s coupled	increasing cellular levels of cAMP
5-HT_5A	G protein coupled; the primary coupling appears to be through Gi/o	inhibiting adenylate cyclase activity.^[3]
5-HT₆	G_s coupled	increasing cellular levels of cAMP
5-HT₇	G_s coupled	increasing cellular levels of cAMP

Specific proteins/genes

Within these general classes of 5-HT receptors, a number of specific types have been characterized:

Summary of characterized 5-HT receptors, with selected high affinity agonist and antagonist ligands
Receptor	Gene	Actions	Agonists	Antagonists
5-HT_1A	HTR1A	CNS: neuronal inhibition, behavioural effects (sleep, feeding, thermoregulation, aggression, anxiety)	buspirone psilocin LSD 8-OH-DPAT	spiperone methiothepin ergotamine yohimbine
5-HT_1B	HTR1B	CNS: presynaptic inhibition, behavioural effects vascular: pulmonary vasoconstriction	ergotamine sumatriptan	methiothepin yohimbine metergoline Risperidone
5-HT_1D	HTR1D	CNS: locomotion, anxiety; vascular: cerebral vasoconstriction	5-(Nonyloxy)tryptamine,^[4] sumatriptan	methiothepin yohimbine metergoline ergotamine
5-HT_1E	HTR1E
5-HT_1F	HTR1F
5-HT_2A	HTR2A	CNS: neuronal excitation, behavioural effects, learning, anxiety smooth muscle: contraction, vasoconstriction / vasodilatation platelets: aggregation	α-methyl-5-HT LSD psilocin DOI	Nefazodone trazodone mirtazapine ketanserin cyproheptadine pizotifen atypical antipsychotics
5-HT_2B	HTR2B	stomach: contraction	α-methyl-5-HT LSD DOI Fenfluramine	yohimbine
5-HT_2C	HTR2C	CNS: anxiety, choroid plexus: cerebrospinal fluid (CSF) secretion	α-methyl-5-HT agomelatine LSD psilocin DOI	mesulergine agomelatine fluoxetine methysergide^[5]
5-HT₃	HTR3A, HTR3B	CNS, PNS: neuronal excitation, anxiety, emesis	2-methyl-5-HT	metoclopramide (high doses) renzapride ondansetron alosetron mirtazapine memantine
5-HT₄	HTR4	GIT: gastrointestinal motility CNS: neuronal excitation, learning, memory	5-methoxytryptamine metoclopramide renzapride tegaserod RS 67333	GR113808 Piboserod
5-HT_5A	HTR5A	CNS (cortex, hippocampus, cerebellum): unknown	5-carboxytryptamine LSD^[3]	unknown
5-HT₆	HTR6	CNS: unknown	LSD	SB271046^[6]
5-HT₇	HTR7	CNS, GIT, blood vessels: unknown	5-carboxytryptamine LSD	methiothepin risperidone

Note that there is no 5-HT_1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT₂ family of receptors and was redesignated as the 5-HT_2C receptor.

Therapeutic modulation

Various drugs are used to modulate the 5-HT system including some antidepressants, anxiolytics, antiemetics, antipsychotics and anti-migraine agents.

External links

Serotonin+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
"5-Hydroxytryptamine Receptors". IUPHAR Receptor Database. International Union of Basic and Clinical Pharmacology. Retrieved 2008-04-11.
Glennon RA, Dukat M, Westkaemper RB (2000-01-01). "Serotonin Receptor Subtypes and Ligands". American College of Neurophyscopharmacology. Retrieved 2008-04-11.
Rubenstein, LA, Lanzara RG (2005-02-16). "Activation of G protein-coupled receptors entails cysteine modulation of agonist binding". Cogprints. Retrieved 2008-04-11.
Frazer A, Hensler JG (1999). "Chapter 13: Serotonin Receptors". In Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD, editors. Basic Neurochemistry: Molecular, Cellular, and Medical Aspects. Philadelphia: Lippincott-Raven. pp. pages 263-292. ISBN 0-397-51820-X. Retrieved 2008-04-11.
Wesołowska A (2002). "In the search for selective ligands of 5-HT₅, 5-HT₆ and 5-HT₇ serotonin receptors" (PDF). Polish Journal of Pharmacology. 54 (4): 327–41. PMID 12523486.

References

↑ Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994). "International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin)". Pharmacol. Rev. 46 (2): 157–203. PMID 7938165.
↑ Marek GJ, Carpenter LL, McDougle CJ, Price LH (2003). "Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders". Neuropsychopharmacology. 28 (2): 402–12. doi:10.1038/sj.npp.1300057. PMID 12589395.
↑ ^3.0 ^3.1 Nelson DL (2004). "5-HT₅ receptors". Current drug targets. CNS and neurological disorders. 3 (1): 53–8. PMID 14965244.
↑ Glennon RA, Hong SS, Dukat M, Teitler M, Davis K (1994). "5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT_1D beta serotonin receptor agonist". J. Med. Chem. 37 (18): 2828–30. doi:10.1021/jm00044a001. PMID 8071931.
↑ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 187
↑ "Target Schizophrenia - Possible future developments". The Association of the British Pharmaceutical Industry. Retrieved 2008-04-11.

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Template:WikiDoc Sources

[pmid7938165-1] Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994). "International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin)". Pharmacol. Rev. 46 (2): 157–203. PMID 7938165.

[pmid12589395-2] Marek GJ, Carpenter LL, McDougle CJ, Price LH (2003). "Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders". Neuropsychopharmacology. 28 (2): 402–12. doi:10.1038/sj.npp.1300057. PMID 12589395.

[Nelson-3] 3.0 ^3.1 Nelson DL (2004). "5-HT₅ receptors". Current drug targets. CNS and neurological disorders. 3 (1): 53–8. PMID 14965244.

[Glennon_et_al_94-4] Glennon RA, Hong SS, Dukat M, Teitler M, Davis K (1994). "5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT_1D beta serotonin receptor agonist". J. Med. Chem. 37 (18): 2828–30. doi:10.1021/jm00044a001. PMID 8071931.

[Rang187-5] Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 187

[titleTarget_Schizophrenia_-_Possible_future_developments-6] "Target Schizophrenia - Possible future developments". The Association of the British Pharmaceutical Industry. Retrieved 2008-04-11.

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